High‐Mobility Group Box 1 (HMGB1) in Angiotensin II induced hypertension

Abstract

Hypertension is the most critical predisposing factor for the development of cardiovascular diseases. While effective pharmacological control of hypertension using angiotensin receptor blockers has been implemented, the clinical course of the disease remains progressive. Consequently, new and innovative approaches for treating hypertension are needed. A growing body of evidence suggests that inflammatory cytokines play important roles in the pathophysiology of cardiovascular disease. Our lab has shown that blocking inflammatory molecules and their transcription factor, nuclear transcription factor kappa B (NF‐kB), within the paraventricular nucleus (PVN) attenuates sympathetic activity and hypertension. However, it remains unknown how inflammation is activated during the development of hypertension. We proposed that the interaction between the inflammatory cytokine protein high‐mobility group box 1 (HMGB1) and its toll‐like receptor, TLR4, results in the up‐regulation of NF‐kB, thereby contributing to the development of hypertension. We performed in vitro and in vivo studies to understand the role played by HMGB1 in the development of hypertension. We treated mouse Neuro‐2a cells with control medium or medium containing Angiotensin II (AngII). Immunofluorescence and immunoblot analysis of AngII‐treated N2a cells correlated increases in HMGB1 levels with up‐regulation of inflammatory markers. In addition, we examined the levels of HMGB1 in the PVN from AngII and saline‐treated rats using RT‐PCR and western blotting. AngII treatment resulted in an increase in blood pressure and this was accompanied by an increase in HMGB1 in the PVN of rats. These findings indicate a potential for HMGB1 in the PVN as a possible mechanism of AngII‐induced hypertension.